As stated in applicants' article entitled "Isolation and Localization of DNA Segments from Specific Human Chromosomes", Proc. Nat'l. Acad. SCI. USA, Vol. 77, No. 5, pp. 2829-2833, May 1980, there are two principal reasons for attempting to achieve as complete as possible fine-structure analysis of the human genome. First, delineation of the DNA sequence of individual genes and construction of the corresponding probes now can be used to detect the presence of human genetic disease. These procedures can be applied in utero so that birth of tragically defective babies can be prevented. Second, and perhaps of even greater importance to biomedical science, definition of DNA sequences over large chromosomal regions, including sequences specifying protein structure as well as the noncoding intervals within and between these sequences, appears to promise greater understanding of physiological and biochemical mechanisms of human gene regulation. The genetic data so obtained should illuminate many aspects of medicine and developmental biology including situations not usually considered to lie within the narrow scope of the term "genetic disease."
Mammalian gene mapping has made significant progress in recent years, particularly by means of cytogenetic identification of relatively gross regions on each chromosome and by development of powerful methods for determining DNA sequences. However, one of these techniques operates at the level of millions of base pairs whereas the other is limited to handling of thousands. Therefore, a large gap in revolving power exists which must be bridged before these techniques can be combined for high-resolution mapping of the human genome. The present invention demonstrates how this gap can be filled.
The recombinant DNA methods used previously isolated and characterized cloned DNA segments based on their ability to code for a specific mRNA. With the novel process described herein, cloned DNA segments can be isolated and characterized based on their genetic map position alone.